Activation of PPARγ by 12/15‑lipoxygenase during cerebral ischemia‑reperfusion injury

Han,Jing; Sun,Li; Xu,Yanwei; Liang,Hao; Cheng,Yan

doi:10.3892/ijmm.2014.1998

Activation of PPARγ by 12/15‑lipoxygenase during cerebral ischemia‑reperfusion injury

Authors:
- Jing Han
- Li Sun
- Yanwei Xu
- Hao Liang
- Yan Cheng
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Affiliations: Department of Neurology, Tianjin Neurology Institute, Tianjin Medical University General Hospital, Tianjin, P.R. China, Tianjin Neurology Institute, Tianjin Medical University General Hospital, Tianjin, P.R. China
Published online on: November 12, 2014 https://doi.org/10.3892/ijmm.2014.1998
Pages: 195-201

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Abstract

Peroxisome proliferator‑activated receptor γ (PPARγ) expression and activity are increased in brain ischemic injury and its agonists have shown potential for brain injury protection. The influence of 12/15‑lipoxygenase (12/15‑LOX) on the activity of PPARγ in oxygen‑glucose deprivation (OGD) and ischemia‑reperfusion (I/R) was investigated. A middle cerebral artery occlusion/reperfusion model with Sprague Dawley (SD) rats was established. For I/R intervention, the rats were treated with the 12/15‑LOX‑derived product 12‑hydroxyeicosatetraenoic acid (12‑HETE) for 30 min before cerebral artery occlusion. Primary cortical neurons from SD rats were used to establish an OGD cell model. 12‑HETE or a 12/15‑LOX antisense oligonucleotide (asON‑12/15‑LOX) was added to OGD‑treated neurons. Western blots, immunofluorescence and enzyme‑linked immunosorbent assays detected protein. Reverse transcription‑polymerase chain reaction analyzed the expression of the PPARγ target genes. PPARγ‑DNA binding activity was determined by peroxisome proliferator responsive element luciferase reporter vectors. 12/15‑LOX total protein increased significantly with I/R, and expression of 12‑HETE was also upregulated. 12‑HETE treatment increased PPARγ protein expression and inhibited inducible nitric oxide synthase protein expression, which was upregulated with I/R. PPARγ nuclear protein and 12/15‑LOX total protein expression in OGD‑treated neurons increased significantly. 12‑HETE treatment increased the expression of PPARγ nuclear protein, upregulated the mRNA levels of PPARγ target genes (lipoprotein lipase and acyl‑CoA oxidase) and enhanced PPARγ‑DNA binding activity. asON‑12/15‑LOX treatment inhibited 12/15‑LOX and PPARγ protein expression and lipoprotein lipase mRNA. Cerebral I/R injury in rats and OGD treatment in neurons promoted 12/15‑LOX expression, and 12‑HETE activated PPARγ. Therefore, PPARγ can be activated by the 12/15‑LOX pathway during cerebral I/R injury.

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